Antifungal prophylaxis in children undergoing hematopoietic stem cell transplantation

Invasive fungal infections (IFI) remain a very important cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT) in children. The recent study from Polish pediatric transplant centers revealed that 27.3% of children transplanted in 2012–2013 developed IFI. The highest risk was observed among patients with AML and ALL after allogeneic HSCT. Such results warrant the use of extensive antifungal prophylaxis in this cohort of patients. ECIL-4 guidelines for antifungal prophylaxis in children undergoing HSCT along with clinical practice are presented in the review. Furthermore preventive measures for patients discharged home after HSCT are discussed

Nonpharmacological interventions targeted at delirium risk factors, delivered by trained volunteers (medical and psychology students), reduced need for antipsychotic medications and the length of hospital stay in aged patients admitted to an acute internal medicine ward : pilot study

Purpose. Effectiveness of nonpharmacological multicomponent prevention delivered by trained volunteers (medical and psychology students), targeted at delirium risk factors in geriatric inpatients, was assessed at an internal medicine ward in Poland. Patients and Methods. Participants were recruited to intervention and control groups at the internal medicine ward (inclusion criteria: age ≥ 75, acute medical condition, basic orientation, and logical contact on admission; exclusion criteria: life expectancy < 24 hours, surgical hospitalization, isolation due to infectious disease, and discharge to other medical wards). Every day trained volunteers delivered a multicomponent standardized intervention targeted at risk factors of in-hospital complications to the intervention group. The control group, selected using a retrospective individual matching strategy (1 : 1 ratio, regarding age, gender, and time of hospitalization), received standard care. Outcome Measures. Hospitalization time, deaths, falls, delirium episodes, and antipsychotic prescriptions were assessed retrospectively from medical documentation. Results. 130 patients (38.4% males) participated in the study, with 65 in the intervention group. Antipsychotic medications were initiated less frequently in the intervention group compared to the control group. There was a trend towards a shorter hospitalization time and a not statistically significant decrease in deaths in the intervention group. Conclusion. Nonpharmacological multicomponent intervention targeted at delirium risk factors effectively reduced length of hospitalization and need for initiating antipsychotic treatment in elderly patients at the internal medicine ward

The "Wholesome Contact" non-pharmacological, volunteer-delivered multidisciplinary programme to prevent hospital delirium in elderly patients : study protocol for a randomised controlled trial

Background: In hospital settings, delirium affects as many as 50% of older patients, aggravating their symptoms and worsening their condition, and therefore increasing the risk of in-hospital complications and death. The aim of this study is to assess the efficacy of structured, non-pharmacological care, delivered to older hospitalised patients by trained volunteers (students of medical fields), on the reduction of incidence of adverse health-related outcomes. Methods/design: This trial will be a randomised, investigator-blind, controlled trial conducted in an internal medicine and geriatric ward in Poland. We aim to include 416 patients who are 70 years of age and have been hospitalised for medical reasons. Eligible patients will be randomised 1:1 to receive structured, non-pharmacological care delivered by students of medicine, psychology and nursing, together with standard medical treatment or standard medical care alone. The protocol of interventions has been designed to cover nine main risk factors for delirium, with the scope of multidisciplinary interventions being individualised and tailored. The protocol will be aimed at immobilisation, vision and hearing impairment, cognitive impairment and disorientation, stress and anxiety, sleep–wake cycle disturbances, dehydration and malnutrition, and pain. A structured evaluation of patients’ cognition, mood, anxiety and functional performance is planned to be carried out twice, on the day of group allocation and at discharge; structured screening assessment for delirium will be conducted daily using the Confusion Assessment Method. The primary outcome will be the incidence of delirium in hospital; secondary outcomes will be in-hospital changes in cognition, mood and anxiety, and functional status, occurrence of falls and death. Discussion: Delirium prevention programmes are being introduced worldwide. A particular novelty of our project, however, is that invitations for voluntary work with older patients at risk for delirium will be addressed to medical students. With the use of the service learning method, the students will shape their attitudes, increase their knowledge and understanding of hospital care, and master competencies to work within interdisciplinary teams, which establishes the originality and practicality of the project

Efficacy and safety of Voriconazole in immunocompromised patients – single centre experience

BackgroundData on epidemiology and survival after fungal infections in patients with cancer are primarily based on studies in adults, whereas few data are available on children.AimThe objective of this study was to determine the safety and tolerability of the oral and i.v. formulations of voriconazole Vfend®, previously not reported in Poland.Materials/MethodsTwenty consecutive children and young adults aged 1 to 25 years, submitted for blood and marrow transplantation (BMT), were recruited during 10 months. When suspected or verified breakthrough systemic fungal infection occurred while kept on primary prophylactic fluconazole regimen, all patients received two loading doses of i.v. or oral voriconazole 6–9 mg/kg every 12 hrs, followed by a maintenance dose of 3 mg/kg every 12 hrs for five doses. If well tolerated, the voriconazole dosage was increased to 4 mg/kg every 12 hrs thereafter.ResultsFungal infection was possible in 15/20, organ involvement with pulmonary process in 13 pts; CNS changes in 2 pts. Fungal aetiology was proven in 3 children (pulmonary Aspergillosis in 2 and Candida krusei in 1 patient), and considered as probable in 2 patients, having lung (2) and CNS (1) involvement. Four patients died. Clinical and radiological improvement was obtained in 14 patients, while uncontrolled, progressive disease occurred in 1 patient. Transient visual disturbances occurred in one patient. Major caution is warranted due to drug interaction via the cytochrome P-450 system which may lead to unexpected toxicity of the coadministered drugs (e.g. Vinca alkaloids, cyclosporine, rifampicin, erythromycin, etc).ConclusionsVoriconazole is an advantageous new azole well tolerated in 20 patients. Outcome in BMT breakthrough infections was good

The impact of NKG2A and NKG2D receptors and HLA-E and MICA ligands polymorphisms on post-transplant complications after paediatric allogeneic HSCT: a single-centre experience

Introduction: Natural Killer cells are the first subpopulation of lymphocytes that reconstitute after allogeneic haematopoietic stem cell transplantation (HSCT). Their activity is regulated by various receptor-ligand interactions, including stimulation of the activating NKG2D receptor by the MICA molecule, and inhibitory NKG2A receptor interacting with the HLA-E. In this study the research effort focused on the effect of selected NKG2A and NKG2D receptors and their ligands (HLA-E and MICA molecules) polymorphisms that may affect the pathomechanisms of post-transplant complications after HSCT in children.Methods: One hundred donor-recipient pairs from a single paediatric transplantation centre were investigated. Altogether six single nucleotide substitutions (NKG2A rs7301582; NKG2D rs1049174, rs1154831; HLA-E rs1264457; MICA rs1051792, rs1063635) were genotyped, and the influence of polymorphisms was analysed on acute and chronic graft-versus-host disease (GvHD), cytomegalovirus (CMV) infection incidence, disease relapse and survival.Results: The distribution of the evaluated polymorphisms did not differ between patients and their donors. The results showed a significant influence of HLA-E rs1264457 polymorphism in patients’ HLA-E*01:01 allele, which was associated with increased risk of CMV infection (p = 0.050), especially in children positive for CMV IgG before transplantation (p = 0.001). Furthermore, the effect of HLA-E*01:01 allele on CMV infections was more evident in children above the age of 7 years (p = 0.031). Strong tendencies (0.05 &lt; p &lt; 0.10) towards association with the risk of acute GvHD were also observed for the NKG2A or MICA polymorphisms of the recipients. In addition, NKG2D rs1154831 AA and MICA rs1063635 GG might play a protective role as they were not present in any recipient who died after transplantation.Conclusion: In summary, there is emerging evidence that genotyping results of NKG2 receptors and their ligands, may have prognostic value for the outcome of paediatric allogeneic HSCT, but more extensive studies performed on larger groups of donors and transplant recipients are required to confirm these observations

Iron overload related diseases and methods of liver iron quantification

Iron overload refers to the excessive accumulation of iron in different organs. It occurs in the course of increased intestinal absorption in hereditary hemochromatosis, repeated blood transfusions, or liver diseases. Excess of iron exerts toxic effect on internal organs leading to liver damage resulting in liver cirrhosis, liver failure, or hepatocellular carcinoma among others. Assessment of liver iron content is essential for diagnosing diseases caused by iron overload and monitoring of iron-reducing therapy. A biopsy is a gold standard of assessment of liver iron concentration; however, new techniques based on the use of magnetic resonance imaging (MRI) gain in importance, as they are non-invasive, reliable, and enable to evaluate iron content in areas inaccessible by biopsy such as brain. This article reviews the currently used methods for assessment of liver iron overload, especially using MRI, in terms of their clinical usefulness and accuracy in different diseases. The authors conclude that assessment of iron overload is difficult, especially in patients with very high or very low level of iron and should be conducted taking into account the patient's clinical condition and the course of primary disease. Increase in the popularity of magnetic resonance signal intensity ratio (SIR) results from its safety, relatively low costs, availability, and possibility to obtain reliable results